This invention relates to a vaccine and serum for immunization against, and treatment for, gram negative bacteria diseases. More specifically, this invention relates to a bacterial mutant of Salmonella enteritidis and its use in a combination vaccine to immunize mammals and birds against diseases caused by endotoxin producing gram negative bacteria in the taxonomic family Enterobacteriaceae. This invention also relates to a detoxified endotoxin immune modulator useful in the treatment of animals and men in combination with other antigens.
In the field of animal husbandry, endotoxin associated diseases pose serious animal health problems and consequently, represent an economic influence of significant proportion.
In horses, endotoxin-associated diseases include founder (i.e., laminitis), colic (i.e., abdominal crisis associated with dietary engorgement and other stressful phenomena such as abdominal obstruction, intestinal ischemia, Gram negative bacterial enteritis/diarrhea, intestinal malabsorption, transport stress, parturition, etc.) septic arthritis, and Gram negative intrautrine infections. Endotoxin-associated diseases in cattle include laminitis in both dairy and feedlot cattle, sudden death syndrome in feedlot cattle, mastitis in dairy cattle, and dysentery, white scours or colibacillosis, and Salmonella diarrhea in baby calves. Endotoxin-associated disease in swine include parturition dysagalactia (i.e., mammary gland failure related to Gram negative endometritis), intestinal edema disease, and baby pig Salmonella diarrhea. Salmonella diarrhea, hemorrhagic septicemia, infection of the air sacs and sinuses; and fowl cholera and other Pasteurelloses are examples of endotoxin-associated diseases of birds.
Previous treatment for endotoxin mediated and/or associated diseases has been retrospective (i.e., after development of clinical illness) and has been limited to cbemotherapeutic intervention. Prevention measures were not achieved with such treatment. Prior limited, definitive, vaccinal protection from Gram negative septicemia and/or endotoxemia has been accomplished only via (a) individualized vaccines comprised of autogenous bacterial isolates expressing various antigenic epitopes (K-antigens or O-carbohydrate side chains) or (b) live vaccines comprised of attenuated or deletion-modified, live bacterial isolates.
The major disadvantage of the current methodologies for treating endotoxin mediated and/or associated diseases is that such treatments are initiated only after clinical illness has developed, which frequently is after the disease has attained an irreversible state. The prior vaccinal protection for Gram negative septicemia and/or endotoxemia that has been reported for individualized vaccines comprised of autogenous bacterial isolates is not time, cost or production efficient because such vaccines are produced retrospectively, after disease has developed.
The primary disadvantages of the polyvalent vaccines comprised of multiple bacterial isolates expressing various antigenic epitopes (K-antigens or O-carbohydrate side chains) are that the bacterial isolates causing disease at any given time are subject to epidemiological shifts and/or drifts in antigenic epitopes causing a change in antigenic specificity and thus loss of protective efficacy. The K-antigens or O-carbohydrate side chains also are potent stimulators of immunoglobulin IgE which is responsible for undesirable anaphylactoid reactions in many animal species, especially the horse.
The primary disadvantages of live vaccines comprised of attenuated or deletion-modified bacterial isolates is that they have the potential for reversion to the wild-type parential strains and thus resumption of pathogenicity for vaccinated animals.
Accordingly, a long felt need exists for a vaccine and serum to immunize and treat against diseases caused by Gram negative bacteria and to overcome the deficiencies found in the prior art. One principal object of this invention is to meet this need.